Do Prognostic Differences Exist Among High-Risk Mutations? A Comparison of Outcomes Between the C634R and Other C634 Mutations in Hereditary Medullary Thyroid Carcinoma.

The American Thyroid Association has stratified C634 mutations as high risk. The association between C634R mutation and a more aggressive medullary thyroid carcinoma (MTC) behavior compared with other C634 mutations remains inconclusive, possibly due to the lack of large cohorts and long-term outcome data. This study aimed to evaluate the aggressiveness and long-term outcomes of hereditary MTC in patients with different codon 634 mutations.

Overview of management and therapeutic advances in medullary thyroid cancer.

Medullary thyroid carcinoma (MTC) is a rare cancer of the thyroid's calcitonin-producing C cells. This review covers recent advances in MTC treatment, emphasizing surgical and systemic therapies. For localized MTC, surgery remains the primary and most effective treatment, with total thyroidectomy and lymph node dissection providing the highest potential for cure.

Association Between Papillary Thyroid Cancer and Primary Aldosteronism in Individuals With Hypertension.

Context: Aldosterone excess chronically induces oxidative stress and cell proliferation. Previously, a single study investigated primary aldosteronism (PA) in patients with papillary thyroid cancer (PTC), albeit without a matched control group.

Objective: We conducted a propensity score-matched, case-control study to investigate the association between PA and PTC in individuals with arterial hypertension (HT).

Identification of Predictors of Metastatic Potential in Paragangliomas to Develop a Prognostic Score (PSPGL).

Context: Paragangliomas (PGLs) are rare tumors in adrenal and extra-adrenal locations. Metastasis are found in approximately 5% to 35% of PGLs, and there are no reliable predictors of metastatic disease.

Objective: This work aimed to develop a prognostic score of metastatic potential in PGLs.

Not Only but and Chromosomal Instability Are Seen in Young Patients with Sporadic Medullary Thyroid Carcinoma.

Context: Genetic analysis of sporadic medullary thyroid carcinoma (MTC) has revealed somatic variants in , , and occasionally other genes. However, around 20% of patients with sporadic MTC lack a known genetic driver.

Objective: To uncover potential new somatic or germline drivers, we analyze a distinct cohort of patients with sporadic, very early-onset, and aggressive MTC.

Is there a role for diagnostic scans in the management of intermediate-risk thyroid cancer?

Radioiodine (RAI) is selectively recommended for intermediate-risk differentiated thyroid carcinomas (DTC). The information gleaned from pretherapy stimulated thyroglobulin levels (sTg) and diagnostic 131I whole-body scans (DxWBS) to guide therapy remains controversial. The present study aimed at evaluating the impact of preablation sTg and DxWBS in the management of intermediate-risk DTC.

Comparison of F-NaF PET/CT with Other Imaging Methods in the Detection of Bone Metastases in Patients with Medullary Thyroid Cancer: a Report of a Series of 31 Cases.

Purpose: To compare the F-NaF PET/CT studies (F-NaF) with other imaging methods in the detection of skeletal metastases (SM) in patients with medullary thyroid cancer (MTC).

Methods: We retrospectively analyzed 31 patients with MTC who performed F-NaF to assess SM. The results of the F-NaF were compared with other imaging methods performed for metastasis detection: Tc-MDP bone scan (BS), magnetic resonance imaging (MRI), contrast-enhanced CT (CT), and Ga-Dotatate and F-FDG PET/CT studies.

Primary hyperparathyroidism as first manifestation in multiple endocrine neoplasia type 2A: an international multicenter study.

Objective: Multiple endocrine neoplasia type 2A (MEN 2A) is a rare syndrome caused by RET germline mutations and has been associated with primary hyperparathyroidism (PHPT) in up to 30% of cases. Recommendations on RET screening in patients with apparently sporadic PHPT are unclear. We aimed to estimate the prevalence of cases presenting with PHPT as first manifestation among MEN 2A index cases and to characterize the former cases.

Burden of metastatic bone disease measured on 18F-NaF PET/computed tomography studies as a prognostic indicator in patients with medullary thyroid cancer.

Purpose: The aim of the study was to assess the association between the burden of metastatic bone disease measured on F-NaF PET/computed tomography (CT) studies and the overall survival (OS) of patients with medullary thyroid cancer (MTC).

Methods: We retrospectively analyzed 31 patients with MTC who performed 18F-NaF PET/CT studies to assess skeletal metastases. The outcomes of the patients (dead or alive) were established based on the last information available on their files.

Is There a Difference Between Minimal and Gross Extension into the Strap Muscles for the Risk of Recurrence in Papillary Thyroid Carcinomas?

The morbidity of papillary thyroid carcinoma (PTC) is primarily related to locoregional recurrences and distant metastases. The definition of minimal extrathyroidal extension (mETE) has been recently revised. The presence of mETE does not impact mortality and is generally not considered to be a predictor for the risk of recurrence.

Quality of Life and Coping in Multiple Endocrine Neoplasia Type 2.

Scarce data are available on the quality of life and psychosocial distress of patients with multiple endocrine neoplasia type 2 (MEN2), a genetic cancer syndrome caused by germline mutations. Carriers of mutations can face several challenges, including fear for the future, guilt for transmission of a germline mutation to an offspring, side effects of cancer treatment, coping behaviors in the face of a chronic and frequently incurable cancer, and difficulties in access to adequate health care. We have addressed the effects of genetic testing on the quality of life of patients with MEN2 and the lifelong physical and psychosocial challenges experienced by these patients.

Genotype and phenotype landscape of MEN2 in 554 medullary thyroid cancer patients: the BrasMEN study.

Multiple endocrine neoplasia type 2 (MEN2) is an autosomal dominant genetic disease caused by RET gene germline mutations that is characterized by medullary thyroid carcinoma (MTC) associated with other endocrine tumors. Several reports have demonstrated that the RET mutation profile may vary according to the geographical area. In this study, we collected clinical and molecular data from 554 patients with surgically confirmed MTC from 176 families with MEN2 in 18 different Brazilian centers to compare the type and prevalence of RET mutations with those from other countries.

Bone and Calcified Soft Tissue Metastases of Medullary Thyroid Carcinoma Better Characterized on F-Fluoride PET/CT than on Ga-Dotatate PET/CT.

Herein, we report a case of a 19-year-old man with multiple endocrine neoplasia type 2B (MEN2B) and medullary thyroid carcinoma (MTC) diagnosed when he was 12 years of age. The patient had previously undergone total thyroidectomy, cervical radiotherapy, and chemotherapy. He progressed with known bone, pulmonary, and lymph node metastases and was scanned with F-fluoride (F-NaF) and Ga-dotatate whole-body positron emission tomography/computed tomography (PET/CT) for metastatic disease monitoring.

Sorafenib for the Treatment of Progressive Metastatic Medullary Thyroid Cancer: Efficacy and Safety Analysis.

Background: Treatment of advanced medullary thyroid carcinoma (MTC) was recently improved with the approval of vandetanib and cabozantinib. However, there is still a need to explore sequential therapy with more than one tyrosine kinase inhibitor (TKI) and to explore alternative therapies when vandetanib and cabozantinib are not available. This study reports the authors' experience with sorafenib as a treatment for advanced MTC.

Intrinsic expression of a multiexon type 3 deiodinase gene controls zebrafish embryo size.

Thyroid hormone is a master regulator of differentiation and growth, and its action is terminated by the enzymatic removal of an inner-ring iodine catalyzed by the selenoenzyme type 3 deiodinase (dio3). Our studies of the zebrafish reveal that the dio3 gene is duplicated in this species and that embryonic deiodination is an important determinant of embryo size. Although both dio3 paralogs encode enzymatically active proteins with high affinity for thyroid hormones, their anatomic patterns of expression are markedly divergent and only embryos with knockdown of dio3b, a biallelically expressed selenoenzyme expressed in the developing central nervous system, manifest severe thyroid hormone-dependent growth restriction at 72 hours post fertilization.

Mice with hepatocyte-specific deficiency of type 3 deiodinase have intact liver regeneration and accelerated recovery from nonthyroidal illness after toxin-induced hepatonecrosis.

Type 3 deiodinase (D3), the physiologic inactivator of thyroid hormones, is induced during tissue injury and regeneration. This has led to the hypotheses that D3 impacts injury tolerance by reducing local T3 signaling and contributes to the fall in serum triiodothyronine (T3) observed in up to 75% of sick patients (termed the low T3 syndrome). Here we show that a novel mutant mouse with hepatocyte-specific D3 deficiency has normal local responses to toxin-induced hepatonecrosis, including normal degrees of tissue necrosis and intact regeneration, but accelerated systemic recovery from illness-induced hypothyroxinemia and hypotriiodothyroninemia, demonstrating that peripheral D3 expression is a key modulator of the low T3 syndrome.

How are childhood thyroid nodules discovered: opportunities for improving early detection.

In a retrospective analysis of childhood thyroid nodules, 18% were radiographic incidentalomas and 41% were discovered by a clinician's palpation; 40% were discovered by patients' families. The latter group had the largest nodules and highest rates of thyroid cancer metastasis, suggesting opportunities for earlier detection through annual well-child visits.

A standardized assessment of thyroid nodules in children confirms higher cancer prevalence than in adults.

Context: Thyroid cancer is the most common endocrine malignancy, but due to its rare occurrence in the pediatric population, the cancer risk of childhood thyroid nodules is incompletely defined, and optimal management of children with suspected nodules is debated.

Objective: The aim was to study the presenting features and cancer risk of sporadic childhood thyroid nodules using a standardized clinical assessment and management plan.

Design And Setting: Boston Children's Hospital and Brigham and Women's Hospital collaborated to create a multidisciplinary pediatric thyroid nodule clinic and implement a standardized assessment plan.

Type 2 iodothyronine deiodinase levels are higher in slow-twitch than fast-twitch mouse skeletal muscle and are increased in hypothyroidism.

Because of its large mass, relatively high metabolic activity and responsiveness to thyroid hormone, skeletal muscle contributes significantly to energy expenditure. Despite the presence of mRNA encoding the type 2 iodothyronine-deiodinase (D2), an enzyme that activates T(4) to T3, very low or undetectable activity has been reported in muscle homogenates of adult humans and mice. With a modified D2 assay, using microsomal protein, overnight incubation and protein from D2 knockout mouse muscle as a tissue-specific blank, we examined slow- and fast-twitch mouse skeletal muscles for D2 activity and its response to physiological stimuli.

Exon 3-deleted genotype of growth hormone receptor (GHRd3) positively influences IGF-1 increase at generation test in children with idiopathic short stature.

Context: A GHR-exon 3 polymorphism has been reported to influence the growth response to hGH therapy in short stature children. None of these studies provided data on IGF-1 generation test.

Objective: To evaluate the influence of the GHR-exon 3 polymorphism on the generation test in children with idiopathic short stature (ISS).